This grant proposal encompasses three major areas related to genetic repair in human subjects. These areas include: (a) variation in repair response to DNA damaging agents as a function of age, (b) investigations of repair capacity in individuals with Systemic Lupus Erythematosis, and (c) the identification of environmental agents that induce repair. In the age-related studies investigations initiated during the previous grant period will be expanded. An analysis will be conducted with cord blood to determine the contribution of the various sub-cell populations to repair, and agents other than 4-Nitroquinoline-Oxide will be used to measure repair response in the various age categories. The repair abnormality detected in the previous grant period with SLE patients will be greatly expanded. Attempts will be made to characterize the abnormal repair response with these patients and studies will be initiated with fibroblast cultures including complementation studies. Patients with associated diseases, such as Discoid Lupus, will also be investigated. The identification of repair-inducing agents may be one of the best techniques that can be carried out in human subjects to identify DNA damaging agents. To determine the applicability of this procedure, certain known alkylating agents used as cancer chemotherapeutics will be evaluated for repair induction both prior and during their use in patients. The repair induction will then be correlated with cytogenetic abnormalities and the presence of active mutagenic substances in the body fluids of treated subjects. Widely used drugs where there is some indication of mutagenic activity, such as Flagyl, will also be evaluated for repair induction in individuals undergoing treatment.